Method and apparatus for non-invasively measuring hemodynamic parameters using parametrics

ABSTRACT

An improved method and apparatus for non-invasively assessing one or more hemodynamic parameters associated with the circulatory system of a living organism. In one aspect, the invention comprises a method of measuring a hemodynamic parameter (e.g., arterial blood pressure) by applanating or compressing portions of tissue proximate to the blood vessel of concern until a desired condition is achieved, and then measuring the hemodynamic parameter. Such applanation effectively mitigates transfer and other losses created by the tissue proximate to the blood vessel, thereby facilitating accurate and robust tonometric measurement. An algorithm adapted to maintain optimal levels of applanation is also described. Methods and apparatus for scaling such hemodynamic parameter measurements based on subject physiology, and providing treatment to the subject based on the measured parameters, are also disclosed.

This application is a continuation of and claims priority to U.S. patentapplication Ser. No. 10/838,404 filed May 3, 2004 of the same title, nowU.S. Pat. No. 7,867,170 which is a continuation of and claims priorityto U.S. Pat. No. 6,730,038, filed Feb. 5, 2002 also of the same title,each of which is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to methods and apparatus for monitoringparameters associated with the circulatory system of a living subject,and specifically to the non-invasive monitoring of arterial bloodpressure.

2. Description of Related Technology

The accurate, continuous, non-invasive measurement of blood pressure haslong been sought by medical science. The availability of suchmeasurement techniques would allow the caregiver to continuously monitora subject's blood pressure accurately and in repeatable fashion withoutthe use of invasive arterial catheters (commonly known as “A-lines”) inany number of settings including, for example, surgical operating roomswhere continuous, accurate indications of true blood pressure are oftenessential.

Several well known techniques have heretofore been used tonon-invasively monitor a subject's arterial blood pressure waveform,namely, auscultation, oscillometry, and tonometry. Both the auscultationand oscillometry techniques use a standard inflatable arm cuff thatoccludes the subject's brachial artery. The auscultatory techniquedetermines the subject's systolic and diastolic pressures by monitoringcertain Korotkoff sounds that occur as the cuff is slowly deflated. Theoscillometric technique, on the other hand, determines these pressures,as well as the subject's mean pressure, by measuring actual pressurechanges that occur in the cuff as the cuff is deflated. Both techniquesdetermine pressure values only intermittently, because of the need toalternately inflate and deflate the cuff, and they cannot replicate thesubject's actual blood pressure waveform. Thus, true continuous,beat-to-beat blood pressure monitoring cannot be achieved using thesetechniques.

Occlusive cuff instruments of the kind described briefly above havegenerally been somewhat effective in sensing long-term trends in asubject's blood pressure. However, such instruments generally have beenineffective in sensing short-term blood pressure variations, which areof critical importance in many medical applications, including surgery.

The technique of arterial tonometry is also well known in the medicalarts. According to the theory of arterial tonometry, the pressure in asuperficial artery with sufficient bony support, such as the radialartery, may be accurately recorded during an applanation sweep when thetransmural pressure equals zero. The term “applanation” refers to theprocess of varying the pressure applied to the artery. An applanationsweep refers to a time period during which pressure over the artery isvaried from overcompression to undercompression or vice versa. At theonset of a decreasing applanation sweep, the artery is overcompressedinto a “dog bone” shape, so that pressure pulses are not recorded. Atthe end of the sweep, the artery is undercompressed, so that minimumamplitude pressure pulses are recorded. Within the sweep, it is assumedthat an applanation occurs during which the arterial wall tension isparallel to the tonometer surface. Here, the arterial pressure isperpendicular to the surface and is the only stress detected by thetonometer sensor. At this pressure, it is assumed that the maximumpeak-to-peak amplitude (the “maximum pulsatile”) pressure obtainedcorresponds to zero transmural pressure.

One prior art device for implementing the tonometry technique includes arigid array of miniature pressure transducers that is applied againstthe tissue overlying a peripheral artery, e.g., the radial artery. Thetransducers each directly sense the mechanical forces in the underlyingsubject tissue, and each is sized to cover only a fraction of theunderlying artery. The array is urged against the tissue, to applanatethe underlying artery and thereby cause beat-to-beat pressure variationswithin the artery to be coupled through the tissue to at least some ofthe transducers. An array of different transducers is used to ensurethat at least one transducer is always over the artery, regardless ofarray position on the subject. This type of tonometer, however, issubject to several drawbacks. First, the array of discrete transducersgenerally is not anatomically compatible with the continuous contours ofthe subject's tissue overlying the artery being sensed. This hashistorically led to inaccuracies in the resulting transducer signals. Inaddition, in some cases, this incompatibility can cause tissue injuryand nerve damage and can restrict blood flow to distal tissue.

Other prior art techniques have sought to more accurately place a singletonometric sensor laterally above the artery, thereby more completelycoupling the sensor to the pressure variations within the artery.However, such systems may place the sensor at a location where it isgeometrically “centered” but not optimally positioned for signalcoupling, and further typically require comparatively frequentre-calibration or repositioning due to movement of the subject duringmeasurement.

Tonometry systems are also commonly quite sensitive to the orientationof the pressure transducer on the subject being monitored. Specifically,such systems show a degradation in accuracy when the angularrelationship between the transducer and the artery is varied from an“optimal” incidence angle. This is an important consideration, since notwo measurements are likely to have the device placed or maintained atprecisely the same angle with respect to the artery. Many of theforegoing approaches similarly suffer from not being able to maintain aconstant angular relationship with the artery regardless of lateralposition, due in many cases to positioning mechanisms which are notadapted to account for the anatomic features of the subject, such ascurvature of the wrist surface.

Another significant drawback to arterial tonometry systems in general istheir inability to continuously monitor and adjust the level of arterialwall compression to an optimum level. Generally, optimization ofarterial wall compression has been achieved only by periodicrecalibration. This has required an interruption of the subjectmonitoring function, which sometimes can occur during critical periods.This disability severely limits acceptance of tonometers in the clinicalenvironment.

One of the most significant limitations of prior art tonometryapproaches relates to incomplete pressure pulse transfer from theinterior of the blood vessel to the point of measurement on the surfaceof the skin above the blood vessel. Specifically, even when the optimumlevel of arterial compression is achieved, there is incomplete and oftentimes complex coupling of the arterial blood pressure through the vesselwall and through the tissue to the surface of the skin, such that themagnitude of pressure variations actually occurring within the bloodvessel is somewhat different than that measured by a tonometric sensor(pressure transducer) placed on the skin. Hence, any pressure signal orwaveform measured at the skin necessarily differs from the true pressurewithin the artery. Modeling the physical response of the arterial wall,tissue, musculature, tendons, bone, skin of the wrist is no small feat,and inherently includes uncertainties and anomalies for each separateindividual. These uncertainties and anomalies introduce unpredictableerror into any measurement of blood pressure made via a tonometricsensor. FIGS. 1 and 2 illustrate the cross-section of a typical humanwrist, illustrating the various components and their relationshipsduring normal (uncompressed) and applanated (compressed) states.

FIG. 3 graphically illustrates the foregoing principles, specificallythe variability in the tonometric measurements relative to the invasive“A-line” or true arterial pressure. FIG. 3 shows exemplary tonometricpulse pressure (i.e., systolic minus diastolic pressure) data obtainedduring applanation of the subject's radial artery to the mean pressure.FIG. 3 demonstrates the differences between the pulse pressures measuredwith the non-invasive prior art tonometric apparatus and the invasiveA-Line catheter; note that these differences are generally neitherconstant nor related to the actual pulse pressure. Hence, there canoften be very significant variance in the tonometrically-derivedmeasurements relative to the invasive catheter pressure, such variancenot being adequately addressed by prior art techniques.

Based on the foregoing, there is needed an improved methodology andapparatus for accurately, continuously, and non-invasively measuringblood pressure within a living subject. Such improved methodology andapparatus would ideally allow for continuous tonometric measurement ofblood pressure which is reflective of true intra-arterial (catheter)pressure, while also providing robustness and repeatability undervarying patient physiology and environmental conditions. Such method andapparatus would also be easily utilized by both trained medicalpersonnel and untrained individuals, thereby allowing certain subjectsto accurately and reliably conduct self-monitoring.

SUMMARY OF THE INVENTION

The present invention satisfies the aforementioned needs by an improvedmethod and apparatus for non-invasively and continuously assessinghemodynamic properties, including arterial blood pressure, within aliving subject.

In a first aspect of the invention, an improved method of obtaining apressure signal obtained from a blood vessel of a living subject usingparametric scaling is disclosed. The method generally comprisesapplanating a portion of tissue proximate to a blood vessel to achieve adesired condition, and measuring the pressure associated with the bloodvessel non-invasively. The measured pressure may then be optionallyscaled using parametric data obtained from the subject (or othersubjects, for example, on a statistical basis). In one exemplaryembodiment of the method, the portion of the tissue (e.g., thatproximate to and effectively surrounding the blood vessel of interest)is applanated or compressed to a level which correlates generally to themaximum pulse pressure amplitude for the blood vessel. This greatlyminimizes the error between the true intra-vessel pressure and thetonometric reading. The tonometric reading is then optionally scaled(adjusted) for any remaining error based on parametric data comprisingthe body mass index (BMI) and pulse pressure (PP) for the subject beingevaluated. In certain cases, such as those where there is little erroror transfer loss resulting from the tissue interposed between the bloodvessel wall and tonometric transducer, little or no scaling is needed.In other cases (e.g., where the transfer loss is significant), scalingof the tonometric pressure reading may be appropriate. In one exemplaryvariant of the method, discrete ranges of parametric data (e.g., BMI/PP)are established such that a given range of data correlates to a unitary(or deterministic) scaling factor or set of factors.

In another exemplary embodiment, a ratio of the BMI to wristcircumference (WC) is formed, and appropriate scaling applied basedthereon.

In a second aspect of the invention, an improved apparatus forapplanating tissue to provide non-invasive blood pressure measurementsis disclosed. The apparatus comprises an applanation element adapted toapply a level of applanation or compression to the tissue proximate tothe blood vessel while also measuring pressure tonometrically. In oneexemplary embodiment, the applanation element comprises a substantiallyrectangular pad having an aperture centrally located therein. Theaperture is a cylindrical shape having one or more pressure transducersdisposed therein and set to a predetermined depth with respect to thecontact surface of the pad. A drive mechanism is connected to theelement to allow varying levels of force to be applied to the tissue.One or more stepper motors with position encoders are employed to permitprecise positioning of the applanation element with respect to the bloodvessel/tissue.

In a third aspect of the invention, an improved method for locating theoptimal applanation for measuring a hemodynamic parameter is disclosed.The method generally comprises varying the position of theaforementioned applanation element relative to the blood vessel suchthat varying hemodynamic conditions within the blood vessel are createdover time. The optimal level of applanation for the element is thendetermined by analyzing data obtained tonometrically from the bloodvessel (i.e., the overlying tissue), the optimal level subsequentlybeing established to monitor the selected parameter. In one exemplaryembodiment, the hemodynamic parameter comprises arterial blood pressure,and the applanation element is varied in position with respect to theblood vessel so as to create a progressively increasing level ofcompression (so-called “applanation sweep”). The optimal applanationoccurs where the highest or maximum pulse pressure is observed. Analgorithm is used to iteratively analyze the pressure waveform obtainedduring the sweep and identify the optimum (maximum pulse pressure)point. The applanation level is then adjusted or “servoed” around thatmaximal point, where additional measurement and processing occurs.Optionally, the foregoing methodology may be coupled with optimizationroutines and positional variations associated with one or more otherdimensions (e.g., lateral, proximal, and angle of incidence with respectto the normal, for the human radial artery), such that all parametersare optimized, thereby providing the most accurate tonometric reading.

In a fourth aspect of the invention, an improved method for scaling theblood pressure measurements obtained from a living subject is disclosed.The method generally comprises: determining at least one physiologicparameter of the subject; forming a relationship between the at leastone parameter and a scaling function; and using the scaling function toscale raw (i.e., unsealed) blood pressure data. In one exemplaryembodiment, the blood pressure measurements are obtained from the radialartery of the subject, and two physiologic parameters are utilized: thefirst parameter comprises the body mass index (BMI) of the subject, andthe second parameter the tonometrically measured pulse pressure (PP). Anindex or ratio of the BMI to the PP is then formed. This index iscompared to a predetermined set of criteria relating the index value tothe required scaling factor to be applied to the raw blood pressuredata. The scaling criteria may be either discrete (e.g., multiple index“bands” having a different scaling factor associated therewith) orcontinuous in nature. The required scaling can be accomplishedautomatically (such as via a look-up table, algorithm or similarmechanism in the system software), or alternatively manually, such asvia a nomograph, graph, or table.

In a second embodiment, the BMI is related to the wrist circumference ofthe subject as determined from the subject. In yet another embodiment,the body fat content of the subject is used to develop a scalingfunction.

In a fifth aspect of the invention, an improved computer program forimplementing the aforementioned methods is disclosed. In one exemplaryembodiment, the computer program comprises an object code representationof a C⁺⁺ source code listing, the object code representation beingdisposed in the program memory or similar storage device of amicrocomputer system. The program is adapted to run on themicroprocessor of the microcomputer system. One or more subroutines forimplementing the applanation optimization and scaling methodologiesdescribed above are included within the program. In a second exemplaryembodiment, the computer program comprises an instruction set disposedwithin the storage device (such as the embedded program memory) of adigital processor.

In a sixth aspect of the invention, an improved non-invasive system forassessing one or more hemodynamic parameters is disclosed. The systemincludes the aforementioned applanation apparatus, along with a digitalprocessor and storage device. In one exemplary embodiment, the apparatuscomprises a pressure transducer disposed in the applanation elementwhich is used to applanate the radial artery of a human. The processoris operatively connected to the pressure transducer and applanationapparatus, and facilitates processing signals from the pressuretransducer during blood pressure measurement, as well as control of theapplanation mechanism (via a microcontroller). The processor furtherincludes a program memory (such as an embedded flash memory) with theaforementioned algorithm stored therein in the form of a computerprogram. The storage device is also coupled to the processor, and allowsfor storage of data generated by the pressure transducer and/orprocessor during operation. In one exemplary variant, the apparatusfurther includes a second storage device (e.g., EEPROM) which isassociated with the transducer and removably coupled to the apparatus,such that the transducer and EEPROM may be easily swapped out by theuser. The removable transducer/EEPROM assembly is pre-configured withgiven scaling data which is particularly adapted for subjects havingcertain parametrics (e.g., BMI within a certain range). In this fashion,the user simply evaluates the parametrics, and selects the appropriateassembly for use with the apparatus. The apparatus supplies anappropriate value of PP (e.g., a “corrected” value derived from recentlyobtained data), thereby generating the BMI/PP ratio needed to enter thescaling function (e.g., lookup table). Once the appropriate scalingfactor is selected, it is automatically applied to the unsealed pressurewaveform. No other calibration or scaling is required, therebysubstantially simplifying operation of the apparatus while allowing forhighly accurate and continuous pressure readings.

In another exemplary variant, the second storage device is configured soas to carry a plurality of scaling factors/functions, the appropriateone(s) of which is/are selected at time of use through parametric datasupplied to the apparatus.

In an seventh aspect of the invention, an improved method of providingtreatment to a subject using the aforementioned methodologies isdisclosed. The method generally comprises the steps of selecting a bloodvessel of the subject useful for measuring pressure data; applanatingthe blood vessel to an optimal level; measuring the pressure data whenthe blood vessel is optimally applanated; scaling the measured pressuredata; and providing treatment to the subject based on this scaledpressure data. In one exemplary embodiment, the blood vessel comprisesthe radial artery of the human being, and the aforementioned methods ofoptimally applanating the blood vessel and scaling the pressure waveformusing BMI/PP are utilized.

These and other features of the invention will become apparent from thefollowing description of the invention, taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional diagram of the wrist area of an exemplaryhuman subject, illustrating the radial artery and other tissue andstructures, in an unapplanated (uncompressed) state.

FIG. 2 is a cross-sectional diagram or the wrist area of FIG. 1,illustrating the effect of tonometric applanation on the radial arteryand structures.

FIG. 3 is a graph illustrating the relationship between thetonometrically obtained pulse pressure and the corresponding invasivecatheter (A-line) pulse pressure for a typical human subject when theradial artery is applanated to mean arterial pressure.

FIG. 4 is a side elevational view of one embodiment of the applanationapparatus of the present invention.

FIG. 4 a is a plan view of the contact pad of the apparatus of FIG. 4,illustrating the relationship between applanation element and pressuretransducer.

FIG. 4 b is a side cross-sectional view of a second embodiment of thecontact pad, illustrating the use of multiple layers of material.

FIG. 4 c is a bottom plan view of a third embodiment of the contact pad,illustrating the use of materials which vary as a function of radiusfrom the center applanation element.

FIG. 4 d is a side plan view of a fourth embodiment of the contact padof the invention, illustrating the use of varying pad materialthickness.

FIGS. 4 e-4 f are bottom and side plan views, respectively, of a fifthembodiment of the contact pad of the invention.

FIGS. 4 g-4 h are bottom and side plan views, respectively, of a sixthembodiment of the contact pad of the invention.

FIG. 5 is a logical flow diagram illustrating one exemplary embodimentof the general method of measuring blood pressure using optimizedapplanation and scaling according to the invention.

FIG. 5 a is a logical flow diagram illustrating one method of scaling anunsealed tonometric waveform using body mass index and pulse pressure.

FIG. 5 b is a graph illustrating a plurality of alternative applanationsweep profiles useful with the present invention.

FIG. 5 c is a graph showing one exemplary method of identifying andeliminating noise artifact from a tonometric pressure waveform using anexternal signal.

FIG. 5 d is a logical flow diagram illustrating one exemplary embodimentof the method of scaling hemodynamic measurements (using BMI and PP)according to the invention.

FIG. 5 e is a graph showing the relationship between BMI/PP and errorfactor for radial artery data derived from a sample of human beings.

FIG. 5 f is a graph showing the relationship between actual anduncorrected tonometric systolic pressure for the sample of FIG. 5 e.

FIG. 5 g is a graph showing the relationship between actual anduncorrected tonometric diastolic pressure for the sample of FIG. 5 f.

FIG. 5 h is a graph showing an exemplary “zero mean” tonometric pressurewaveform before and after being corrected (scaled).

FIG. 5 i is a logical flow diagram illustrating a second exemplaryembodiment of the method of scaling hemodynamic measurements (using BMIand WC) according to the invention.

FIG. 6 is a graphical representation of a first embodiment of anomograph useful for scaling blood pressure measurements according tothe methodology of FIG. 5 h.

FIG. 7 is logical flow diagram illustrating one exemplary method forlaterally positioning the applanation apparatus of FIG. 4 according tothe invention.

FIGS. 7 a-7 b are graphs illustrating pulse pressure (PP) versus lateralposition for the first and second lateral position sweeps of the methodof FIG. 7, including the relative location of the PP maxima therein.

FIG. 7 c is a graph of PP versus lateral position illustrating aspurious artifact (pressure peak) due to motion of the subject duringmeasurement.

FIG. 7 d is a graph of PP versus lateral position illustrating a PPprofile having no clear maximum.

FIG. 8 is a block diagram of one exemplary embodiment of the apparatusfor measuring hemodynamic parameters within the blood vessel of a livingsubject according to the invention.

FIG. 8 a is a side plan view of an exemplary unitary transducer/storagedevice assembly useful with the apparatus of FIG. 8.

FIG. 9 is a logical flow diagram illustrating one exemplary embodimentof the method of providing treatment to a subject using theaforementioned methods.

DETAILED DESCRIPTION OF THE INVENTION

Reference is now made to the drawings wherein like numerals refer tolike parts throughout.

It is noted that while the invention is described herein primarily interms of a method and apparatus for assessment of hemodynamic parametersof the circulatory system via the radial artery (i.e., wrist) of a humansubject, the invention may also be readily embodied or adapted tomonitor such parameters at other blood vessels and locations on thehuman body, as well as monitoring these parameters on other warm-bloodedspecies. All such adaptations and alternate embodiments are readilyimplemented by those of ordinary skill in the relevant arts, and areconsidered to fall within the scope of the claims appended hereto.

As used herein, the term “hemodynamic parameter” is meant to includeparameters associated with the circulatory system of the subject,including for example pressure (e.g., diastolic, systolic, pulse, ormean pressure). The term “physiologic parameter” is meant to includemeasurements or quantities associated with the physiology subject,including for example the subject's weight, height, body mass index(BMI), wrist circumference, ankle circumference, or body fat content,but may also include one or more “hemodynamic” parameters previouslydefined herein (e.g., blood pressure, etc.).

Additionally, it is noted that the terms “tonometric,” “tonometer,” and“tonometery” as used herein are intended to broadly refer tonon-invasive surface measurement of one or more hemodynamic parameterssuch as pressure, such as by placing a sensor in communication with thesurface of the skin, although contact with the skin need not be direct(e.g., such as through a coupling medium or other interface).

The terms “applanate” and “applanation” as used herein refer to thecompression (relative to a state of non-compression) of tissue, bloodvessel(s), and other structures such as tendon or muscle of thesubject's physiology. Similarly, an applanation “sweep” refers to one ormore periods of time during which the applanation level is varied(either increasingly, decreasingly, or any combination thereof).Although generally used in the context of linear (constant velocity)position variations, the term “applanation” as used herein mayconceivably take on any variety of other forms, including withoutlimitation (i) a continuous non-linear (e.g., logarithmic) increasing ordecreasing compression over time; (ii) a non-continuous or piece-wisecontinuous linear or non-linear compression; (iii) alternatingcompression and relaxation; (iv) sinusoidal or triangular wavesfunctions; (v) random motion (such as a “random walk”; or (vi) adeterministic profile. All such forms are considered to be encompassedby the term.

Lastly, the terms “processor” and “digital processor” are meant toinclude any integrated circuit or other electronic device (or collectionof devices) capable of performing an operation on at least oneinstruction including, without limitation, reduced instruction set core(RISC) processors such as those manufactured by ARM Limited ofCambridge, UK, CISC microprocessors, central processing units (CPUs),and digital signal processors (DSPs). The hardware of such devices maybe integrated onto a single substrate (e.g., silicon “die”), ordistributed among two or more substrates. Furthermore, variousfunctional aspects of the processor may be implemented solely assoftware or firmware associated with the processor.

Overview

In one fundamental aspect, the present invention comprises a method ofaccurately measuring one or more hemodynamic parameters using optimalapplanation and scaling of raw or unsealed measurements. In generalterms, such applanation mitigates transfer loss and other errorsintroduced by non-invasive (e.g., tonometric) measurement techniques asapplied to the complex system of blood vessels, tissue, muscle, and skinat the location of measurement of the hemodynamic parameter. Forexample, as will be described in greater detail below, the presentinvention is useful for accurately measuring the blood pressure using atonometric or surface pressure sensor disposed over the radial artery ofa human being, the measured pressure waveform potentially varyingsubstantially from that actually experienced within the radial arteryitself. In one embodiment, a specially configured applanation(compression) apparatus is disclosed, wherein an applanation element isutilized to compress or bias the tissue and accordingly, the bloodvessel contained therein. This applanation apparatus advantageously withassociated pressure transducer may be used alone as described in detailherein, or in conjunction with literally any type of other apparatusadapted for hemodynamic parameter measurement, including for example thedevices described in co-pending U.S. patent application Ser. Nos.09/815,982 entitled “Method and Apparatus for the Noninvasive Assessmentof Hemodynamic Parameters Including Blood Vessel Location” filed Mar.22, 2001, and 09/815,080 entitled “Method and Apparatus for AssessingHemodynamic Parameters within the Circulatory System of a LivingSubject” also filed Mar. 22, 2001, both of which are assigned to theassignee hereof and incorporated herein by reference in their entirety.

Since the signal under measurement (e.g. pressure) is time variant,iteration and optimization are selectively utilized within the algorithmembodying the methodology of the present invention to account for thisvariation. Specifically, the signal is time variant over the shortperiod of the cardiac cycle, over the longer period of the respiratorycycle, and potentially over the even longer or shorter period ofhemodynamic changes resulting from varying drug concentrations andvolume changes. Accordingly, the algorithm described herein utilizes theaforementioned applanation mechanism to continually find and maintainthe optimal level of applanation, thereby maintaining an environmentconducive for accurate, continuous, and non-invasive parametricmeasurement.

It will further be noted that the optimal bias technique of the presentinvention can be used in conjunction with lateral (transverse),proximal, or other positioning techniques to help locate the pressuretransducer(s) over the blood vessel of interest. To this end, any numberof different positioning approaches may be employed either alone or incombination (where compatible). For example, the lateral positioningbased on analysis of the pressure signal obtained by a tonometric sensordisposed generally over the blood vessel (described subsequently herein)may be utilized. Alternatively, the primarily acoustic lateralpositioning and wall detection approaches described in theaforementioned co-pending applications may be used. As yet anotheralternative, manual location and positioning of the applanators andtransducer over the selected blood vessel may be employed.

Applanation Apparatus for Pressure Measurement

Referring now to FIGS. 4-4 a, a first embodiment of the applanationapparatus of the invention is described in detail.

The ability to accurately measure the pressure associated with a bloodvessel depends largely upon the mechanical configuration of theapplanation mechanism. Under the typical prior art approaches previouslydiscussed, the pressure transducer comprises the applanation mechanismsuch that the mechanism and transducer are fixed as a single unit.Hence, the pressure transducer experiences the full force applied todeform the tissue, structures, and blood vessel. This approach neglectsthe component of the applantion force required to compress thisinterposed tissue, etc. as it relates to the pressure measuredtonometrically from the blood vessel. Conversely, under no compression,the magnitude of the pressure within the blood vessel is attenuated ormasked by the interposed tissue such that the pressure measuredtonometrically is less than that actually existing in the vessel(so-called “transfer loss”).

In contrast, the apparatus of the present invention embodies thepressure transducer disposed within an applanation element, the latterhaving a specially designed configuration adapted to mitigate theeffects of such transfer loss in a simple, repeatable, and reliable waysuch that it can be either (i) ignored or (ii) compensated for as partof the tonometric measurement. As discussed in greater detail below, theshape, size, placement, and selection of materials for the applanationelement can be important in determining the amount of transfer lossexperienced under a given set of conditions. Specifically, these factorslargely dictate the relationship between the maximum pulse pressure andthe mean pressure, and hence ultimately the error associated with agiven tonometric pressure reading.

As shown in the exemplary embodiment of FIG. 4, the applanation element402 is used to compress the tissue generally surrounding the bloodvessel 404 of interest, and to apply force to the blood vessel wall soas to begin to overcome the wall or hoop stress thereof. The applanationelement (or applanator) 402 is coupled to a drive motor 406 whichprovides the compressive applanating force 408 in reaction to thepatient via a wristband or brace 410 (or an external surface). Theapplanator 402 of the illustrated embodiment includes a generallyrectangular applanator body 414 with a substantially cylindricalprojection 412 (see FIG. 4 a), and a contact pad 441 disposed on thebottom surface thereof. The body 414 is molded from a polymer (e.g.,polycarbonate) for ease of manufacturing, rigidity, and low cost,although other materials may be chosen. A substantially cylindricalaperture 415 is formed centrally in the contact pad 441 to receive thebody projection 412. Accordingly, when the contact surface 440 of theapplanator pad 441 is pressed against the skin of the patient, agenerally rectangular contact area (“footprint”) with a central apertureresults.

A pressure transducer 422, disposed substantially over the blood vessel404 and received within an aperture 413 of the applanator body 414, isused to obtain tonometric pressure readings from the surface of the skin(tissue) overlying the blood vessel. The height of the active face 420of the transducer 422 is set within its housing 417 so as to provide thedesired degree of coupling between the transducer face and tissue whenthe applanator 402 is compressed onto the subject's tissue. It will berecognized, however, that the transducer 422 or it's housing 417 may bemade adjustable or movable within the aperture 413 so as to facilitateoptimal positioning under different operating conditions and/or toaccommodate different subject physiologies.

As shown in FIG. 4, a thin polymer layer 423 is also applied over thetop of the transducer face 420 so as to (i) couple the transducer facemore positively to the tissue; and (ii) level the surface contacting thetissue formed by the transducer face, the body projection 412, and thetransducer housing 417. Specifically, a layer of a pliable, compressiblesilicone based compound (e.g., silicone rubber) is formed over thetransducer face 420 within the housing 417 as shown, although othermaterials may be used. In addition to its superior physical propertiesand excellent pressure signal coupling from the tissue to the transducerface 420, the silicone layer 423 also allows for some degree ofvariation in the distance between the transducer face and the topsurface 419 of the housing 417 during manufacture, since the silicone is“filled” to the appropriate depth to provide a level and effectivelycontinuous top surface.

The motor 406 of the applanator assembly is, in the present embodiment,rigidly coupled to the wrist brace assembly 410 so as to provide asubstantially invariant platform against which the motor may exertreaction force while applanating the subject's tissue. This “rigid”configuration is utilized so as to avoid any significant compliance ofthe assembly as the motor 406 drives the contact pad 441 in compressionof the tissue/blood vessel during applanation. This rigidity isadvantageous from the standpoint that helps allow the pressuretransducer 422 to record the maximum value of pulse pressure (or otherselected parameter); greater degrees of compliance in the mechanism tendto reduce the magnitude of the peak pressure observed, therebypotentially making the identification of the pulse pressure peak moredifficult.

It will be recognized, however, that alternate configurations having atleast some degree of compliance may be utilized in some applications.For example, in one alternate embodiment, a rigid coupling of theapplanator assembly to the wrist brace 410 is used; however, a somewhatflexible applanator body 414 with a curved interior surface (not shown)that can adapt to the curvature of the subject's wrist may be utilized.In this fashion, the coupling remains rigid, but the applanator bodycomplies in a limited fashion to the subject's wrist curvature, therebyallowing for a substantially uniform level of contact across a broaderportion of the wrist. The degree of compliance of the body 414 iscontrolled by its flexural strength; i.e., the level of force needed toincrementally deform the body increases as a function of its complianceor “bending”, thereby effectively limiting its total compliance, andcausing the contact pad 441 mated thereto to preferentially compressafter a certain degree of deformation occurs. Other alternatives readilyfashioned by those of ordinary skill may be used as well.

Advantageously, any number of different wrist brace configurations maybe used consistent with present invention. For example, the bracedisclosed in Assignee's co-pending U.S. patent application Ser. No.09/815,982 previously incorporated herein by reference may be used.Other configurations may also be substituted with equal success, suchconfigurations being readily fashioned by those of ordinary skill in themechanical arts.

This foregoing flexibility in wrist brace configuration also underscoresanother benefit of the present invention, specifically that theaforementioned applanation mechanism (and associated technique describedin detail below) is somewhat less sensitive to variations in attitude ofthe applanator and pressure transducer relative to the surface of thesubject's skin than prior art techniques and apparatus. This comparativeinsensitivity relates in part due to the fact that pressure is coupledthrough the tissue and blood vessel wall over a fairly broad range ofarc with respect to the longitudinal axis of the blood vessel, such thatangular misalignment (i.e., angles of pressure transducer incidencewhich depart from a vector normal to the skin's surface at the point ofmeasurement) has less effect. Furthermore, since the first applanationelement 402 contacts a broad area of tissue around the blood vessel andcompresses/distorts it to some degree, some angular misalignment orrotation of the applanation element contact surface 440 with respect tothe skin surface can be tolerated.

The contact pad 441 of the applanation element 402 is formed in thepresent embodiment of a compressible, pliable foam-like cellularurethane material marketed by Rogers corporation as Poron™, althoughother materials with similar qualities may be used in conjunction withor in place of the Poron disclosed herein. Poron has, among otherproperties, a desirable durometer characteristic which is well adaptedto the present application. The contact pad 441 is made approximately0.25 in. (6.35 mm) thick, although other thicknesses may be used. TheAssignee hereof has noted during various field trials that the Poronmaterial provides excellent physical properties with respect to thecompression of the subject's tissue and blood vessel, thereby veryeffectively mitigating the aforementioned transfer losses associatedwith these structures. Additionally, the contact pad 441 of the presentembodiment is made replaceable by the user/subject so as to permitmaintenance of a hygienic (or even sterile) environment. For example,the pad 441 may be replaced for each use, along with replacement of thepressure transducer assembly, or for each different subject if desired.The use of a low cost polymer advantageously makes the cost ofmaintaining the device quite low.

It will further be appreciated that while the contact pad 441 describedabove and showed in FIG. 4 a is made of both substantially constantthickness and uniform material composition, either of these parametersmay be varied for specific applications. For example, the pad 441 can beconstructed using a multi-layer or “sandwich” approach, with thephysical properties of the various layers being varied so as to providecertain properties for the overall pad assembly. In one embodiment, atwo-layer pad (FIG. 4 b) having different compression constants for eachlayer is used to provide a progressively varying compression of the pad;e.g., one layer of material will preferentially compress first, followedby the second layer when the incremental compression force of the firstlayer exceeds that of the second layer. In another embodiment, thematerial properties are varied in a generally radial direction withrespect to the center aperture so as to provide varying rates ofcompression as a function of radius from the contact point with thetissue overlying the blood vessel (FIG. 4 c). In yet another embodiment(FIG. 4 d), the thickness of the pad is varied as a function of spatialposition so as to provide varying rates of tissue compression.

Based on the foregoing, it will be appreciated that the configuration ofthe pad 441 may be “tuned” as needed to accomplish specific rates oftissue compression and/or provide other desired performance attributes.The design and fabrication of such alternate embodiments is well knownto those of ordinary skill in the mechanical and materials arts, andaccordingly is not described further herein.

Additionally, while the embodiments of FIGS. 4-4 d comprise asubstantially planar, rectangular pad 441 with a centrally locatedaperture having a circular cross-section, it will be recognized thatother shapes and/or configurations may be used. For example, as shown inthe embodiment of FIGS. 4 e-4 f, the pad 451 of the applanation elementcomprises a circular cross-sectional shape with a slight concave arcformed in the contact surface 450 such that the pad conforms to theinterior surface of the wrist 455. As yet another alternative (FIGS. 4g-4 h), the applantion element pad may be configured a set of discretelateral pads 460 disposed on either side of a multi-element array 463 ofpressure transducers 464. Myriad other combinations of applanatorshapes, sizes, footprints, planarities, and configurations may be usedconsistent with the present invention, all such combinations fallingwithin the scope of the claims appended hereto.

The motors 406 used in the illustrated embodiment of FIG. 4 to drive theapplanation element 402 is a precision “stepper” motor of the type wellknown in the motor arts. This motor also includes one or more positionencoders (not shown) which provide an electrical signal to the hostsystem processor and associated algorithm to very precisely control theposition of the applanation element during operation. Accordingly, asdescribed in greater detail below, the variable used in the presentembodiment to represent applanation element position is the number ofmotor steps (positive or negative relative to a “zero” point); thisapproach advantageously removes the need to measure the absoluteposition with respect to the subject's tissue or anatomy. Rather, therelative number of steps is measured via the position encoder; and thisis effectively correlated to pressure measurement obtained from thepressure transducer(s).

A detailed discussion of the electronic and signal processing apparatusused to support the operation of the applanation mechanism 400 of FIG. 4is provided with respect to FIG. 7 below.

Methodology

Referring now to FIG. 5, the general methodology of optimallyapplanating or compressing the blood vessel and local tissue utilizingthe previously described apparatus is described in detail.

As previously discussed, one fundamental concept of the presentinvention (and hence the methodology presented below) is to control theapplanation element 402 such that the transfer loss associated with thetissue and structures surrounding the blood vessel is mitigated duringmeasurement. In the case of the human radial artery, the transfer lossis effectively mitigated at that level of applanation where thetonometrically measured pulse pressure is maximized. Too littlecompression, and the coupling between the blood vessel wall and tissuesurface (and hence transducer active surface) is incomplete, yieldingtonometric pressure values which are significantly in error. Too muchcompression, and the vessel wall collapses, thereby distorting thecross-sectional shape of the vessel significantly, and again producinghigh levels of error. The optimal condition is to couple the vessel wallthrough the interposed tissue as completely as possible withoutotherwise affecting the hemodynamics of the vessel itself.

As shown in FIG. 5, the first step 502 of the method 500 comprisesplacing the applanation mechanism 400 in the position with respect tothe subject's blood vessel. Such placement may be accomplished manually,i.e., by the caregiver or subject visually aligning the transducer anddevice over the interior portion of the wrist, by thepressure/electronic/acoustic methods of positioning previouslyreferenced, or by yet other means. Ideally, the applanation element 402and its contact pad will be comfortably situated transversely over theinterior of the wrist, with the transducer element 422 directlyoverlying the radial artery with little or no inclination with respectthereto. The element 402 and transducer 422 may be laterally aligned(step 504) and proximally aligned (step 506) if required. In oneexemplary embodiment, the tonometrically measured pressure signalobtained from the transducer 422 may be used as a basis for suchlateral/proximal positioning, in a manner similar to that used fordetermining optimal applanation level (described in detail below).

Once the applanation element 402 is suitably located and oriented, theelement 402 is operated per step 508 so as to applanate the tissuesurrounding (and at least partly overlying) the blood vessel to adesired level so as to identify an optimal position where the effects oftransfer loss and other errors associated with the tonometricmeasurement are mitigated. Specifically, as shown in the embodiment ofFIG. 5 a, an applanation sweep is commenced (step 530) using the motor406 driving the element 402, thereby progressively increasing thepressure applied to the tissue by the contact pad 441. During thissweep, the pressure waveform obtained from the transducer 422 isanalyzed on an interval (e.g., per-beat) basis per step 532 so as todetermine the value of pulse pressure for that interval. Suchcalculations are generally accomplished within such a short duration(owing largely to the signal processing apparatus described below withrespect to FIG. 7) with respect to the rate of change of applanationsuch that the necessary calculations can be made “on the fly” during theapplanation sweep. Certain artifacts or conditions existing within thewaveform are identified (step 534), thereby indicating that the desiredlevel of applanation has been reached. For example, in the embodiment ofFIG. 5 a, the pulse pressures are calculated for each contiguous heartbeat interval. “Peak-to-trough” amplitude values of the waveform foreach interval are determined as part of this calculation in the presentembodiment, although other quantities and/or portions of the waveformmay be utilized. Where the calculated pulse pressure decreases below acertain percentage (e.g., 50%) of a prior beat for a designated numberof beats (e.g., two), a pulse pressure “maximum” is declared, and levelof applanation is reduced back to that corresponding to the prior beatinterval where pulse pressure was maximized (step 510 of FIG. 5).

The coarse positioning of the applanation element 402 back to theposition of maximum pulse pressure is accomplished in one embodimentusing the motor position recorded during the applanation sweep (e.g., ata given number of motor steps which corresponds to the level of arterialapplanation or compression where maximum pulse pressure was detected).Once the coarse position is obtained and the applanator returned to thisposition, the system then is permitted to “settle” for a period of time,and an iterative “search” approach is utilized to vary the position ofthe applanation motor and element in each direction; i.e., moreapplanation and less applanation, while monitoring mean pressure asdetermined from the pressure transducer 422 (and supporting circuitry).A “maximum” detection routine is utilized as part of this iterativemovement to verify that in fact the maximum point has been achieved and,if required, move the applanation element to that point from the currentposition. It is noted that while the motor position or similar indiciacorresponding to the maximum pulse pressure is generally a good “coarse”positioning determinant, other factors (physiologic and otherwise) maycause the level of optimal applanation to vary somewhat, therebynecessitating the maximum detection routine referenced above for bestresults. However, depending on the level of accuracy desired, the“coarse” repositioning criteria may be used alone if desired.

It will be recognized that a variety of different applantion sweepprofiles may be employed as part of the foregoing steps. Specifically,the simplest profile is probably the straight linear rate sweep, whereinthe applanation element drive motor 406 is controlled by the systemcontroller (described below) to move the applanation element at aneffectively constant rate (e.g., 5000 motor steps/min). This produces anon-linear application of force or bias to the tissue being compressed,since more force will be required to compress the tissue as it isnearing full compression as opposed to the onset of applanation. Asanother alternative, the applantion sweep may be step-wise linear; i.e.,a contiguous set of mini-sweeps of constant rate punctuated by finitepause periods of no motion. This approach may be useful wheresignificant signal processing or other data processing/acquisition isrequired during the applanation sweep.

As yet another alternative, the rate of applanation may be madedeterministic. For example, in one alternative embodiment, the rate iscoupled to the patient's heart rate, which is determined either directlyby the hemodynamic measurement system (i.e., extracted from the pressurewaveform measured by the pressure transducer 422 through signalprocessing), or by another apparatus (such as an electrocardiographicdevice adapted to analyze the QRS complexes of the heart). Specifically,in one embodiment using the indigenous determination via the measuredpressure waveform, the extracted heart rate is entered into a linearequation of the form y=mx+b, such that for a high subject heart rate,the rate of applantion is set proportionately high, and vice versa.Clearly, however, non-linear functions may be substituted if desired.FIG. 5 b graphically illustrates a number of the foregoing alternatives.

Additionally, other deterministic quantities may be used as the basisfor the applanation rate determination. For example, the values ofsystolic and/or diastolic blood pressure (or derivations thereof) may beused as inputs to an applanation rate equation. Myriad other variantsmay also be used, either alone or in combination, so as to best selectthe proper applanation rate under varying subject physiologicconditions.

Next, per step 512 of the method 500 of FIG. 5, the desired pressurevalue(s) are measured and stored in the system's storage device,discussed below, while the applanation is set at (or servoes around)that point where pulse pressure is maximized. For example, in oneembodiment, the systolic and diastolic waveforms are extracted from thepressure transducer output signal. It is noted that in the case of theexemplary human radial artery, the point of applanation at which maximumpulse pressure occurs correlates strongly to mean arterial bloodpressure, with the degree of correlation being affected to some degreeby the shape, size, footprint, compliance, and other properties of thecontact pad 441 previously described herein with respect to FIG. 4.

Next, in step 514, the measured values of the hemodynamic values (e.g.,pressure) are optionally scaled or corrected for transfer loss asappropriate. It will be recognized that not every measured value willneed to be scaled, and in some cases no scaling will be required. Thisresult stems from the fact that (i) different individuals have differentphysiologic features and construction, thereby allowing the transferloss associated with one individual to be markedly different fromanother; and (ii) the magnitude of the transfer loss (and hence theerror in the tonometric measurement as compared to the actualintra-vascular pressure) may be small so as to be inconsequential. Aswill be described in subsequent discussion herein, there is a strongcorrelation between the magnitude of the transfer loss for a givenindividual and their body mass index (BMI), thereby allowing the presentinvention to, inter alia, “intelligently” scale the raw measuredhemodynamic parameters.

It is noted that the present invention may also utilize the heart ratesignal provided by the aforementioned ECG or other external device as asynchronization signal to aid in identifying artifacts or other featuresin the tonometrically obtained pressure waveform. Specifically, sincethe ECG (or other) non-indigenous measurement technique used may not besubject to non-physiologic noise (e.g., movement by the patient,vibration of the treatment facility, low-frequency AC noise, etc.),artifacts present in the pressure waveform can be mapped against theexternal signal for purposes of correlating and eliminating suchartifacts. For example, as is well known, the aforementioned ECGtechnique uses electrical signals relating to the QRS complex of thesubject's heart for measuring heart rate; the ECG waveform willtherefore register QRS complexes at the interval they are generated bythe subject's heart, largely irrespective of motion artifact or othernoise. Hence, wherein the tonometric pressure waveform will displaymotion artifact (such as the gurney on which the subject is lying beinginadvertently kicked by someone administering treatment, or theambulance in which the subject is riding traversing a rough patch ofroad) to some degree, such artifacts will generally be absent from theECG signal. The present invention optionally maps the two signalscoincident in the temporal dimension using the digital processordescribed below with respect to FIG. 7, and examines the signals at apredetermined rate and interval (e.g., a moving 100 ms window every 100ms), or upon the occurrence of a predetermined event (e.g., ECG QRSamplitude exceeding a given threshold) to determine whether an observedpressure transient should be included in the data collected for thatperiod, or discarded as a spurious noise transient or motion artifact.In one exemplary embodiment (FIG. 5 c), the ECG waveform is monitoredfor the detection of each heart beat; a windowing function f(t) isapplied to the tonometrically obtained waveform data to effectivelyblock out pressure transients occurring outside the specified temporalwindow, which is centered on the ECG-detected “beat”. Hence, only thoseartifacts which are coincident with heart beats as detected by the ECGwill be included in the subsequent signal processing of the tonometricwaveform. Assuming a random distribution of noise/artifact, the greatmajority of such noise/artifact will be eliminated from the pressurewaveform using such a technique.

It will be appreciated, however, that other functions and approaches tocorrelating the external signal (ECG or otherwise) and the tonometricwaveform may be used. For example, rather than a windowing approachwhich has two discrete states (i.e., discard or not discard), moresophisticated signal processing and filtration algorithms adapted toselectively identify noise/artifact and remove it from the waveform “onthe fly” may be employed. Such algorithms are well known to those ofordinary skill in the signal processing arts, and accordingly are notdescribed further herein.

BMI/Pulse Pressure (PP) Scaling

Referring now to FIGS. 5 d-5 h, one exemplary embodiment of themethodology for scaling or correcting raw or unsealed hemodynamic dataobtained using the methodology of FIG. 5 described above. It will berecognized that while the embodiment of FIGS. 5 d-5 h is described interms of an algorithm such as would be utilized in conjunction with adigital computer system having a microprocessor or signal processor, themethod of the present invention may be partially or even entirelypracticed independent of such an algorithm or computer system. Forexample, portions of the algorithm may be accomplished via hardware(such as gate logic embodied in an ASIC or FPGA), or even manually viadirect or indirect control of the operator. Accordingly, the exemplar ofFIGS. 5 d-5 h is merely illustrative of the broader concepts.

As illustrated in FIG. 5 d, the method of scaling 514 generallycomprises first determining a first physiologic parameter of the livingsubject under evaluation (step 540). For the sake of illustration, themethod 514 is described in terms of the scaling of a tonometricallyobtained blood pressure measurement obtained from the radial artery of ahuman being, although it will be appreciated that the method may beemployed at other monitoring locations on the same or different species.The first parameter obtained in this exemplary embodiment comprises abody mass index (BMI) of the type well known in the medical arts.Specifically, the BMI comprises:

BMI=W/H²  (Eqn. 1)

where:

BMI=Body mass index (Kg/m)

W=Subject weight (kgf)

H=Subject height (m)

Typical BMI values for the human species range from about 15 Kg/m² up toroughly 50 Kg/m², although values outside this range may occur. Thevalues of subject weight (W) and height (H) are readily obtained usingconventional measurement techniques not described further herein.

Next, a second physiologic parameter of the same subject is determinedin step 542. In the method embodiment of FIGS. 5 d-5 h, the pulsepressure (i.e., the systolic pressure minus the diastolic pressure) isused in conjunction with the body mass index (BMI) of the subject togenerate a corrected pulse pressure.

FIG. 5 e illustrates the relationship (based on empirical data derivedby the Assignee hereof, discussed in greater detail below) between theratio of BMI to tonometrically measured pulse pressure (PP) and theerror factor (percentage error between tonometrically derived pressurereading, and the actual intravascular pressure as determined by A-lineinvasive catheter). As shown in FIG. 5 e, the relationship between errorand BMI/PP is well grouped and substantially linear for the datapresented, the latter spanning a broad range of BMI/PP values.

FIG. 5 e is significant from the standpoint that it provides adescription of the behavior of error as a function of certain selectedphysiologic parameters (e.g., BMI and PP). This description allows thepresent invention to apply the appropriate level of scaling to thetonometric pressure measurements to correct for transfer loss andrelated errors present in these measurements. As shown in FIG. 5 e, thelosses (as reflected by the error factor) at low BMI/PP values are low,and increase (linearly) as BMI/PP increases. In practical terms, personswith high BMI for the same PP value will require more transfer losscorrection, which intuitively follows from the observation that suchpeople commonly have a greater mass of tissue (skin, fat, muscle,tendon, etc.) interposed between the radial artery and surface of theskin on the interior of the wrist. Conversely, a very tall, thin personwith average PP value will require little correction for transfer loss,which is also intuitively compelling.

FIGS. 5 f and 5 g illustrate the relationship between actualintravascular pressure (as measured, for example by an A-line) andtonometrically measured pressure for systolic and diastolic pressures,respectively, for the empirical data previously referenced. As shown ineach of these figures, the data is tightly grouped along a functionalline (here, modeled as linear). Stated differently, there arepredictable functional relationships between the tonometrically measuredsystolic and diastolic pressures and their corresponding actualintravascular values.

In the present embodiment, a linear relationship is also used to modelthe percentage error between the tonometric and actual intravascularpressures, as follows:

$\begin{matrix}{{\% \mspace{14mu} {Error}} = {\frac{{PP}_{T} - {PP}_{A}}{{PP}_{T}} = {{M \cdot \frac{BMI}{{PP}_{T}}} + b}}} & \left( {{Eqn}.\mspace{14mu} 2} \right)\end{matrix}$

Where:

PP_(T)=pulse pressure (tonometric)

PP_(A)=pulse pressure (actual)

M=slope

b=intercept

Manipulating this equation, the following is obtained:

PP_(T)−PP_(A) =M·BMI+b·PP_(T)  (Eqn. 3)

PP_(T) −b·PP_(T) −M·BMI=PP_(A)  (Eqn. 4)

and

PP_(T)(1−b)−M·BMI=PP_(A)  (Eqn. 5)

Eqn. 5 is the generalized relationship relating the actual intravascularpressure (PP_(A)) and the tonometric pressure (PP_(T)) based on BMI.Note that PPA (also referred to as the corrected pulse pressure, PP_(C))is based on the current interval (e.g., beat), while PP_(T) is based onan average pulse pressure over the prior “n” pulses. Here, “n” can beany number (e.g., 10), or made deterministic such as being based onanother quantity measured from the subject or otherwise derived in thecalculation process if desired. Hence, in effect, the ratioPP_(C)/PP_(T) is the scale factor which is applied to subsequent samplesof the tonometrically obtained pressure waveform. An “n” interval movingwindow is established, wherein the same scale factor is applied overeach interval (beat).

Despite the use of a linear relationship in Eqn. 5 above (and thefunctions of FIGS. 5 f and 5 g), it will be appreciated that therelationship between the BMI/PP and error factor (or for that matter anyother physiologic parameters or function thereof used for scaling) neednot be linear or assume any prescribed form. For example, data collectedon the population as a whole or subsets thereof (e.g., those within aspecific BMI range) may be decidedly non-linear. Furthermore, otherparametric relationships such as the BMI/WC approach described below mayyield a non-linear function, which can be used as the basis for scaling.Alternatively, the function may be piecewise-continuous or evendiscontinuous. Myriad functional relationships therefore may besuccessfully substituted and used consistent with the general premise ofthe present invention.

Returning to FIG. 5 d, the corrected (scaled) pressure waveform is nextderived per step 544. In the present embodiment, this is determined by(i) subtracting the average “n” pulse tonometrically measured meanpressure from each subsequent tonometric sample value of pressure (a“zero mean” sample result) per step 546; (ii) multiplying each “zeromean” sample value derived in (i) by the derived scale factor (step548), and adding back the “n” beat average mean pressure value (step550); and (iii) repeating the process every “n” beats, using a newlyderived scale factor for every “n” beats (step 552). The resultantwaveform is a scaled waveform which is effectively corrected fortransfer loss.

Note that the foregoing “zero mean” approach is used so as to zero orcenter the waveform around a known reference level (zero). In thisfashion, systolic pressure measurements advantageously will always beabove the zero mean, and diastolic pressure measurements always below.However, a non-zero mean (i.e., offset) or other reference point may bechosen if desired, such as any value between zero and the measuredpressure mean. The zero-mean approach is merely an expedient conventionto simplify analysis and make the results more intuitive to theuser/operator. It will be appreciated that such value(s) may be chosento facilitate computational efficiency, especially in more “thin”hardware environments where computational capacity of the host platformis minimal or at a premium. For example, a low cost (or even disposable)apparatus embodying the present invention may have a digital processorwith very limited MIPS and/or memory; the mean or offset point cantherefore be chosen so as to best optimize this limited capability.

It is also noted that the magnitude of error associated with thetonometric measurements described herein is always negative (FIG. 5 d isentirely on the “negative” side of the error factor scale). Thiscorrelates to the tonometric pressure always being less than the actualintravascular pressure in magnitude due to transfer loss. When this factis coupled with the “zero mean” technique described above, it results intonometric systolic and diastolic pressure values which always must beincreased in magnitude during sealing (“stretched up” for systolic, and“stretched down”, as shown in FIG. 5 h). As described in greater detailbelow with respect to FIG. 7, the apparatus 700 of the present inventioncalculates a “stretch” value based on BMI and PP according to thepreviously discussed methodology which performs this stretching of thetonometric waveform so as to comply with the actual intravascularwaveform.

The use of pulse pressure (PP) as a physiologic parameter in the presentembodiment provides the further advantage of being derived from othervariables measured by the pressure transducer. That is, PP is derived bya mathematical manipulation of the systolic and diastolic pressurevalues at any given time (or over a predetermined interval);accordingly, in the exemplary embodiment of the invention wherein thescaling factor determination is performed algorithmically using pressurevalues obtained intrinsically by the system during pressure measurement,there is no need for the caregiver or subject to measure such parameter.This advantageously simplifies the scaling process.

As previously noted, the data presented above was obtained by theAssignee while conducting clinical trials in validation of themethodology of the present invention. Specifically, the Applicantselected a number (>20) of individuals at random, and obtained multipletonometric waveforms for each. This generated in excess of 500 datafiles relating to these individuals. Each data file was broken into aplurality of “epochs” (e.g., 10-beat increments), with the pressurevalue being averaged over each epoch. The aforementioned BMI-basedscaling was applied to each averaged epoch, with all scaled epochsultimately being collectively analyzed to generate “global” ornon-individual specific data. The radial artery of one arm of eachindividual was arbitrarily chosen as the basis for the measurements,while the other arm of the same individual(s) was utilized to providesubstantially concurrent A-line invasive catheter measurements of bloodpressure. Results of this “proof of principles” testing yielded very lowerrors in both systolic and diastolic measurements of roughly −1.2 mmHg(std. deviation=8.6) and −2.6 mmHg (std. deviation 5.4), respectively,after scaling as compared to the corresponding A-line values, therebyvalidating the methodology experimentally. Note that based on therequired +/− 5 mmHg (std. deviation=8 mmHg) performance level of thewell known AAMI SP10 standard relating to auscultation/oscillometricblood pressure measurement techniques, the clinical performance of thepresent invention is excellent.

BMI/WC Scaling

Referring now to FIG. 5 i, a second exemplary embodiment of the methodof scaling (step 514 of FIG. 5 d) is described. In this secondembodiment, the second physiologic parameter comprises the circumferenceof the subject's wrist (WC) at the point of measurement. This isfunctionally related to the BMI previously described to produce ascaling index, as described in greater detail below.

In the first step 562 of the method of scaling 560 of FIG. 51, the BMIvalue is obtained for the subject as previously described herein withreference to FIG. 5 d. Next, in step 564, the BMI value determined instep 562 is related to the second parameter (e.g., wrist circumferenceof the same subject) to obtain a scaling index I_(s) as defined by Eqn.6:

I _(s)=BMI/WC  (Eqn. 6)

where:

I_(s)=Scaling factor (considered dimensionless)

BMI=Body mass index (Kg/m²)

WC=Wrist circumference (cm)

“Typical” values for I_(s) range from approximately 2 to 10, althoughvalues outside this range may be observed. Note, however, that the term“typical” here refers to values observed over a broad cross-section ofthe general population, and variations in body type, bone size, weight,body fat content, and the like may cause significant variations in I_(s)between two individuals.

From the scaling index value I_(s) determined for each individual, ascale factor K_(s) is next determined (step 566). Table 1 belowillustrates one exemplary approach used to derive the scaling factorK_(s) from the scaling index I_(s). This table is derived from empiricaldata obtained by the Assignee during clinical trials of a statisticallysignificant number of individuals, as compared toauscultation/oscillometry (“cuff”) measurements obtained from the sameindividuals.

TABLE 1 Scale Index (I_(s)) Scale Factor (K_(s)) Remarks >4.0 1.2 (20%)Significant fatty tissue present at radial artery 3.3-4.0 1.09 (9%) Somefatty tissue present at radial artery <3.3 1.0 (no scaling) Little fattytissue present at radial arteryThe embodiment of Table 1 has the advantage of simplifying the K_(s)determination process, since the K_(s) value to be applied to themeasured blood pressure of the subject is chosen from a limited numberof discrete intervals (i.e., I_(s) value ranges). For example, considerthe subject having an I_(s) value of 2.8. Using Table 1, it can be seenthat no scaling of the raw blood pressure measurement is required. Thisrelates primarily to the subject having a comparatively large wristcircumference in relation to their BMI, often indicating the absence ofsignificant amounts of fatty tissue at the measurement site (i.e.,radial artery). Less fatty tissue provides more complete “coupling”(less transfer loss) between the pressure transducer and the bloodvessel wall, thereby requiring less corrective scaling.

In contrast, consider the individual with an I_(s) value of 6.0. Forthis individual, Table 1 indicates that a scale factor K_(s) of 1.2should be applied (effectively correcting the observed pressure valueupward by 20 percent). Such scaling is needed since the transfer lossfor this individual is substantially greater, as reflected in thegreater ratio of their body mass index (BMI) to their wristcircumference. Hence, the BMI (numerator) tends to drive or be directlyrelated to the amount of fatty tissue present at the subject's wrist.

Lastly, in step 568, the scale factor K_(s) is applied to the raw oruncorrected blood pressure measurement to obtain a scaled or correctedmeasurement. This is accomplished in the illustrated embodiment bysimply multiplying the uncorrected pressure measurement by the scalefactor K_(s). For example, an unsealed value of 100 mmHg and a K_(s) of1.2 would result in a corrected pressure value of 120 mmHg. Aspreviously noted with respect to the BMI/PP embodiment described above,the tonometrically measured value will in effect always be less thantrue intravascular pressure, and accordingly the tonometric value willalways be scaled upwards in magnitude.

It will be recognized that while the embodiment of Table 1 above isrendered in terms of a small number (three) of discrete scale indexintervals, other numbers of intervals (whether equal in magnitude ornot, or companded) may be utilized to impart a greater degree ofprecision or granularity to the pressure scaling correction process. Forexample, ten (10) intervals arranged in a logarithmic relationship couldbe utilized. As yet another alternative, other parameters may be used toqualify or substantiate the scaling process. For example, after thescaling factor K_(s) is determined using Table 1 (or similar), theproposed scaling factor could be cross-checked against a statisticaldatabase for other individuals or sub-classes of individuals (e.g.,those with BMI above a certain value). In this fashion, data “outliers”can be identified before the scaling is applied, potentially instigatingthe caregiver to obtain a confirmatory measurement or consult otherresources.

Note that since the method of FIG. 5 i is at least in the presentembodiment somewhat heuristic, very precise measurement of this secondparameter is not critical. Accordingly, precise location of themeasurement on the subject's wrist is similarly not critical. Thisunderscores a significant advantage of the present methodology, in thatthe resulting scaling applied to the un-scaled pressure measurement issubstantially insensitive to errors in the clinician's or caregiver'swrist circumference measurements. This advantage also exists withrespect to the BMI determination of step 1002 previously described,since the BMI determination is fairly insensitive to errors inmeasurement of the subject's height and/or weight.

Alternatively, other physiological parameters may be utilized to “scale”the waveform (or scaling factor K_(s) before it is applied to the rawpressure measurement). For example, it is well known that the electricalimpedance of a subject's tissue in a given region of the body can berelated to the body mass of the subject. Typically, such measurementsare made using electrical signals at high frequencies (e.g., 100-200kHz) so as to overcome noise and other deleterious effects present atlower frequencies. Hence, the present invention may utilize such anelectrical impedance measurement obtained from the subject's wrist orarm as a basis for determining body mass (or a BMI-equivalentparameter), the latter being used to scale the tonometric pressurewaveform. Such measurements may also be used in a confirmatory capacityto qualify the scale factor derived by other means, and/or provideadditional granularity within a given discrete range of scale factor.

In another embodiment, the relationship between the scale factor K_(s)and the scale index I_(s) is determined using a nomograph as illustratedin FIG. 6. As shown in FIG. 6, the nomograph 600 comprises a series ofvertical scales 602, 604, 606, 608, 610, 612, 614 which are disposed inparallel relationship to one another on a planar surface (e.g.,laminated card, paper, or the like), not shown. In the illustratedembodiment, the vertical scales comprise a weight scale 602, a heightscale 604, a BMI scale 606, a wrist circumference (WC) scale 608, ascale index (I_(s)) scale 610, a measured (raw) blood pressure scale612, and an actual or scaled blood pressure scale 614. The variousscales are aligned so as to permit sequential determination of theparameters of interest relating to the scaled blood pressuredetermination methodology described above. For example, the twoleft-hand scales 602, 604 are entered (using the data obtained from thesubject) and, using a straight-edge such as a ruler, the BMI valuedetermined by aligning the straight-edge to intersect the weight andheight scales 602, 604 at the values obtained for each from the subject.The BMI value is then read off of the third (BMI) scale 606 where thestraight edge intersects that scale 606. The construction of suchnomographic scales is well known in the mathematical arts, andaccordingly is not described further herein.

In the nomograph 600 of FIG. 6, the remaining scales (WC, scale factor,measured blood pressure, and corrected blood pressure) are disposedadjacent to the weight, height, and BMI scales to facilitate calculationof the corrected blood pressure. Specifically, after calculating the BMIas previously described, the user simply places the straight-edge on thenomograph such that the edge intersects the BMI and WC scales 606, 608at the determined BMI value and actual WC value of the subject,respectively. The scale factor K_(s) is then determined as being thepoint of intersection of the edge and the scale factor scale 610.Continuing in similar fashion, the user then subsequently aligns thestraight-edge such that it intersects the scale factor and raw bloodpressure scales 610, 612, thereby intersecting the corrected pressurescale 614 at the value of the true (corrected) blood pressure. Usingsuch scales on the same nomograph 600, the present invention allows theuser to “walk” the straight edge across the nomograph 600, therebyobviating the need to record or even remember the results ofintermediary calculations. Specifically, for example, after the BMI iscalculated, the user simply pivots the straight edge around the point ofintersection of the straight edge and the BMI scale 606 until the WCscale 608 is properly intersected, thereby yielding the scale factor.Similarly, the user then pivots the straight edge around the point ofintersection of the edge and the scale factor scale 610, and so forth.The user accordingly need never even know the values of BMI or scalefactor determined in these intermediary steps; rather, they need onlyremember (or record) the corrected blood pressure vale from the lastscale 614. However, a table 625 for recording the intermediary values(and the initial data obtained from the subject) is optionally providedto facilitate calculation and record keeping. With respect to thelatter, the nomograph 600 may be reproduced on a sheet of paper which islayed upon a flat surface. The caregiver simply obtains the weight,height, and WC data from the subject, enters it into the applicablespace in the table 625, and then can easily refer to the date whenconducting the aforementioned nomographic determinations. After thesedeterminations are mad, the caregiver records the results in theappropriate spaces of the table 625, and then saves the entire sheet inthe subject's file or other location. In this fashion, the bloodpressure determination can be advantageously reconstructed at a laterdate, thereby providing accountability and error identification.

It will be appreciated that the foregoing nomograph 600 of FIG. 6 canalso be rendered or reduced to a “wheel” calculator configuration of thetype well known in the art (not shown). Such wheel comprises one or morestationary and moving wheels, typically fabricated from a flexiblelaminated material, which rotate around a central spindle. The peripheryor surfaces of the wheels are coded such that when various portions ofthe wheel are aligned (representing various values of the aforementionedparameters), the resulting value can be directly read off of anotherportion of a wheel. Such devices have the advantage of not requiring useon a flat surface, thereby allowing (i) the user significant mobility,and (ii) preventing the lack of a flat surface or straight edge frompotentially distorting the results of the calculation. Yet otherconfigurations may also be used consistent with the invention.

It will further be appreciated that the scales of the nomograph 600 asdescribed above may be made discrete or continuous in nature, consistentwith the desired application of the scaling factors. Hence, thefunctionality represented in Table 1 above may be readily made innomographic form, or alternatively, a continuous, non-discreterepresentation (i.e., with I_(s) and K_(s) being continuous variables)may be made with equal ease.

Lastly, it is noted that the nomographic technique described above mayalso be applied if desired to the BMI/PP method previously described,the calculations of Eqns. 1-5 above being reduced to a nomographicrepresentation by one of ordinary skill in the mathematical arts.

In yet another embodiment of the method of FIG. 5 i, the relationshipbetween the scale factor K_(s) and the scale index I_(s) is determinedalgorithmically via an embedded code within the processor or storagedevice of the blood pressure measurement apparatus (e.g., see discussionrelating to FIG. 7 below). For example, the relationships of Table 1above can be readily reduced to an algorithm or computer program (suchas an assembly language program compiled from a C-based source codelisting using an assembler) which performs the aforementioneddeterminations via the digital processor. A look-up table or similarstructure can also be coded within the algorithm if desired. Thisalgorithmic embodiment has the distinct advantage of obviating theaforementioned nomograph or similar device, and making the bloodpressure correction process transparent to the user. Once properlyqualified, the use of software code also reduces the risk of error inthe scaling determination, since no misalignment of the straight-edge orsimilar error can occur. The coding and implementation of such algorithmis readily accomplished by those of ordinary skill in the computerprogramming arts, and accordingly is not described further herein.

Results of the various intermediary steps (i.e., BMI, scale factordetermination) may also be optionally displayed on any display deviceassociated with the system, and stored within the storage device orother desired location (or transmitted to a remote location such as viaa computer network) to facilitate additional analysis.

It will further be recognized that the BMI/PP and BMI/WC methodologiesmay be combined and/or used in a confirmatory fashion to complement eachother. For example, the scaling factor (and/or corrected blood pressure)determined using the aforementioned WC-based technique can be validatedor checked using the PP-based technique, or vice versa. Alternatively,the results of the PP and WC-based techniques may be averaged oranalyzed statistically. Many such permutations and combinations arepossible consistent with the teachings of the present invention.

Lateral Search Methodology

Referring now to FIG. 7, the methodology of lateral positioning of thetransducer assembly of the applanator 402 is described. As previouslydiscussed, it is desirable to properly place the transducer 422 directlysuperior to the blood vessel of concern (e.g., radial artery) prior toperforming the optimal applanation, measurement, and scaling proceduresdiscussed above. Such proper lateral placement helps ensure a high levelof coupling between the blood vessel wall and transducer face, and insome regards helps to mitigate transfer loss.

As shown in FIG. 7, the exemplary method 700 of the illustratedembodiment comprises first positioning the applanator element 402 (andhence the pressure transducer 422) generally over the blood vessel ofinterest per step 702 as previously described with respect to FIG. 5.The applanator element 402 is held within a brace or other apparatussuch that the former is positioned generally over the inside surface ofthe subject's wrist. It is noted that the present method anticipatessome degree of lateral misalignment.

Next, in step 704, the level of applanation for the applanator 402 isadjusted so as to maintain a substantially constant pressure readingfrom the transducer 422. This adjustment comprises “servoing” around thedesignated pressure to as to closely maintain the constant targetpressure. This pressure is selected so as to provide adequate signalcoupling between the artery wall and the active face of the transducer(via the interposed tissue and coupling layer 423), while alsopermitting movement of the transducer 422 (and the coupling layer 423)across the surface of the subject's skin without undue friction ordistortion of the tissue which might be painful to the subject, or causeanomalies in the measured pressure waveform.

The applanator 402 is then moved laterally across the subject's wrist toa starting position which is offset from the blood vessel of concern(step 706). For example, in one embodiment, the applanator 402 is movedtoward the lateral portion of the subject's wrist, more proximate to theradial bone (and specifically the styloid process). It will berecognized, however, that other starting positions (e.g., medial orotherwise) may be used. The applanator 402 is positioned using a lateralpositioning stepper motor 845 (see discussion of FIG. 8 below) which iscoupled to the applanator 402. However, such positioning may beaccomplished using any type of motive force, and may even be performedmanually if desired.

Once the applanator 402 is positioned at its starting point, the pulsepressure (PP) is monitored (step 708) based on the systolic anddiastolic components obtained from the pressure waveform of thetransducer 422.

Next, in step 710, a lateral position sweep is commenced using thelateral positioning motor 845, the latter drawing the applanator 402(and pressure transducer 422) across the surface of the subject's skinwhile servoing in the sagittal direction to maintain the aforementionedpredetermined pressure. In the present embodiment, a linear positionsweep; i.e., constant rate of travel across the surface of the wrist, isutilized, although it will be appreciated that as with the applanationsweep previously described, other profiles (non-linear or otherwise) maybe employed. Pulse pressure is measured during the sweep of step 710,and the data stored for analysis.

The sweep rate is selected so as to permit sufficient collection ofpressure waveform data and calculation of the PP per unit time,therefore providing the desired level of granularity for PPmeasurements. Specifically, if the sweep rate is too high, only a few PPdata points will be generated, and the lateral position accuracy will bedegraded. Conversely, if the sweep rate is too slow, positionallocalization using PP will be high, but the localization process will belong, thereby extending the time required to ultimately obtain a bloodpressure measurement.

The sweep of step 710 continues until (i) a predetermined position forthe applanator 402 relative to the starting position is achieved; and/or(ii) a pulse pressure maximum is observed. Other criteria forterminating the first lateral position sweep may also be utilized. FIG.7 a illustrates an exemplary PP versus lateral position profile obtainedusing the method 700.

Once the lateral sweep of step 710 is completed, a second lateral sweepin the opposite direction is completed (step 712). As shown in FIG. 7 b,this second sweep back-tracks over the first sweep and again recordsmeasured PP as a function of time and/or position. In one embodiment,the second sweep operates over a smaller region (i.e., smaller lateraldistance) than the first sweep, and at a slower rate to achieve a moreprecise location for the artery. Similar criteria for terminating thesecond sweep as to those used in the first sweep (step 710) areemployed.

Once the second sweep (step 712) is completed, the data collected forboth sweeps is analyzed (step 714) to determine if a true PP maximum hasbeen observed. Specifically, each set of data are analyzed to determineif the maximum PP value occurs at a lateral position (as determined by,e.g., the stepper motor position encoding) corresponding to that for theother sweep, within a prescribed error band. If the PP maxima are wellcorrelated, there is a high confidence that one of the two maxima (or aposition there between) comprises the true position where PP maximumpressure would be measured. Conversely, if the two maxima are not wellcorrelated, additional data gathering (sweeps) may be needed to resolvethe ambiguity and/or more accurately localize the desired lateralposition for the transducer 422.

In addition to maxima which are not well correlated in position, lateralsweep profiles with multiple local maxima and/or artifacts may beobserved. As shown in FIGS. 7 c-7 d, movement by the subject duringsweep or other sources may induce noise within the PP profile(s),thereby frustrating the identification of the true maximum position. Inthe present embodiment, the occurrence of multiple or no maxima (asdetermined by, e.g., a mathematical analysis of each interval of thesweep relative to the others) will disqualify a given lateral sweep fromconsideration, and necessitate additional sweeps (step 716). Signalprocessing algorithms capable of identifying artifacts and maxima/minimawithin pressure waveforms are well known in the art, and accordingly arenot described further herein.

It is also noted that a “statistical mode” of operation may be employedwith respect to the above-described method 700. Specifically, aplurality of lateral position sweeps may be conducted before theanalysis of step 714 is performed, with a corresponding (or lesser)number of those sweeps being included in the analyzed data set. In thisfashion, artifacts or noise which is present in one sweep may not bepresent in the next, and therefore will have less degrading effect onthe ultimate position determination. Signal processing and/orstatistical analysis may be performed to the resulting data as desired.

Furthermore, the method of FIG. 7 (and the apparatus of FIG. 8 below)may be configured so as to localize in an iterative fashion around acalculated position. For example, each lateral positioning sweep isanalyzed at its completion, and the results of the maximum locationanalysis used to localize the spatial region for subsequent sweep(s).Specifically, in one embodiment, the PP data obtained from the firstlateral position sweep is analyzed, and the maximum PP locationidentified. Based on this information, the lateral positioning motor isrepositioned (in the direction of motion opposite to the original sweep)to the beginning of a position window centered around the detectedmaximum PP location. A second, reduced duration “mini-sweep” is thenconducted while the PP is measured, and the PP data subsequentlyanalyzed at completion of the mini-sweep to identify the maximum PPlocation. Correlation analyses such as those previously described hereinmay or may not be applied as desired, to determine the correlationbetween the maximum PP locations identified in each sweep. This processmay be continued if desired to more accurately locate the maximum PPlocation. It may also be performed periodically during continuous bloodpressure monitoring (i.e., after the optimal applanation level has beendetermined and any necessary waveform scaling applied, per FIG. 5 above)if desired, so as to account for patient movement, slippage, etc.Specifically, the system may take a lateral positioning “time out”,wherein the controller causes the applanation motor 406 to retract theapplanator 402 to the predetermined constant pressure level (step 704 ofFIG. 7), and one or more lateral update sweeps performed.

It will be recognized that myriad different permutations of theforegoing steps (i.e., compression to a desired level, movement of theapplanator 402 laterally across the blood vessel, and analysis of themaxima) may be utilized consistent with the present invention. All suchpermutations and modifications to this methodology are, given thedisclosure provided herein, within possession of those of ordinary skillin the art.

System Apparatus for Hemodynamic Assessment

Referring now to FIG. 8, an apparatus for measuring hemodynamicproperties within the blood vessel of a living subject is now described.In the illustrated embodiment, the apparatus is adapted for themeasurement of blood pressure within the radial artery of a human being,although it will be recognized that other hemodynamic parameters,monitoring sites, and even types of living organism may be utilized inconjunction with the invention in its broadest sense.

The exemplary apparatus 800 of FIG. 8 fundamentally comprises theapplanation assembly 400 of FIG. 4 (including element 402 and pressuretransducer 422) for measuring blood pressure from the radial arterytonometrically; a digital processor 808 operatively connected to thepressure transducer(s) 422 (and a number of intermediary components) for(i) analyzing the signals generated by the transducer(s); (ii)generating control signals for the stepper motor 406 (via amicrocontroller 811 a operatively coupled to the stepper motor controlcircuits); and (iii) storing measured and analyzed data. The motorcontrollers 811, processor 808, auxiliary board 823, and othercomponents may be housed either locally to the applanator 402, oralternatively in a separate stand-alone housing configuration ifdesired. The pressure transducer 422 and its associated storage device852 are optionally made removable from the applanator 402 as describedin greater detail below with respect to FIG. 8 a.

The pressure transducer 422 is, in the present embodiment, a strain beamtransducer element which generates an electrical signal in functionalrelationship (e.g., proportional) to the pressure applied to its sensingsurface 421, although other technologies may be used. The analogpressure signals generated by the pressure transducer 422 are convertedinto a digital form (using, e.g., an ADC 809) after being optionallylow-pass filtered 813 and sent to the signal processor 808 for analysis.Depending on the type of analysis employed, the signal processor 808utilizes its program (either embedded or stored in an external storagedevice) to analyze the pressure signals and other related data (e.g.,stepper motor position as determined by the position encoder 877,scaling data contained in the transducer's EEPROM 852 via I2C1 signal,etc.).

As shown in FIG. 8, the apparatus 800 is also optionally equipped with asecond stepper motor 845 and associated controller 811 b, the secondmotor 845 being adapted to move the applanator assembly 402 laterallyacross the blood vessel (e.g., radial artery) of the subject asdescribed above with respect to FIG. 7. Operation of the lateralpositioning motor 845 and its controller 811 b is substantiallyanalogous to that of the applanation motor 406, consistent with themethodology of FIG. 7.

As previously discussed, continuous accurate non-invasive measurementsof hemodynamic parameters (e.g., blood pressure) are highly desirable.To this end, the apparatus 800 is designed to (i) identify the properlevel of applanation of the subject blood vessel and associated tissue;(ii) continuously “servo” on this condition to maintain the bloodvessel/tissue properly biased for the best possible tonometricmeasurement; and (iii) scale the tonometric measurement as needed toprovide an accurate representation of intravascular pressure to theuser/operator. During an applantion “sweep”, the controller 811 acontrols the applanation motor 406 to applanate the artery (andinterposed tissue) according to a predetermined profile, such as thatdescribed with respect to FIG. 5. Similarly, the extension andretraction of the applanation element 402 during the later states of thealgorithm (i.e., when the applanation motor 406 is retracted to theoptimal applanation position, and subsequent servoing around this point)are controlled using the controller 811 a and processor 808. Theapparatus 800 is also configured to apply the scaling methodologiesprevious discussed with respect to FIGS. 5 d-5 i. Specifically, asdiscussed with respect to FIG. 5 d above, the corrected (scaled)pressure waveform is derived by (i) subtracting the average “n” pulsetonometrically measured mean pressure from each subsequent tonometricsample value of pressure (a “zero mean” sample result); (ii) multiplyingeach “zero mean” sample value derived in (i) by the derived scalefactor, and adding back the “n” beat average mean pressure value; and(iii) repeating the process every “n” beats, using a newly derived scalefactor. The resultant waveform is a scaled waveform which is effectivelycorrected for transfer loss.

In an alternate implementation, a “stretch” calculation is performedaccording to Eqn. 7 after the applanation sweep and optimization processhas been completed:

P _(ts) =P _(tu)+(P _(th) ×S _(BMI))  (Eqn. 7)

Where:

P_(ts)=“stretched” or corrected tonometric pressure

P_(tu)=uncorrected tonometric pressure

P_(th)=uncorrected tonometric pressure (high-pass filtered)=

S_(BMI)=BMI stretch factor

This function effectively generates the corrected tonometric pressuredata by adding the uncorrected pressure data to a high-pass filteredcomponent of the uncorrected data which has been scaled by the BMIstretch factor. Based on empirical data, the BMI stretch factor in thepresent embodiment is set to range from between approximately 0.0 to+0.6, although other values may be used.

Note that during an applantion sweep of the “stretch” calculation, thescaling functionality described above is automatically turned off (withauto “on” feature” as well) since no scaling is required during theprocess of identifying the artifact of concern (e.g., maximum pulsepressure point). Additionally, the user/operator is permitted todetermine the minimum cutoff value for the hemodynamic parameter (e.g.,pressure) for the applanation sweep. A default value is set at 90 mmHg,although other values may be substituted. This minimum cutoff helpsprevent the system from spuriously or erroneously triggering on aninvalid event (e.g., a “false” maximum which may result at low pressurevalues due to the system configuration).

When the apparatus 800 begins data acquisition, a routine is optionallyinitiated which calculates the coefficients for the system's4^(th)-order high pass filter (with a cutoff frequency of 0.1625 Hz,which is selected to eliminate any DC component present in the signal.Additionally, for each data block (i.e., each group of data associatedwith a given monitoring interval), the apparatus 800 performs a parallelcalculation of highpass filter tonometric data for the “stretch”calculation.

The present embodiment also includes a beat detection algorithm. When anew beat is detected (based on processing of the tonometric pressurewaveform), a software call is made to update the BMI-determined stretchfactor. If the subject's BMI information has not yet been entered, thensystem simply updates the (pulse) pressure history for futurecalculations.

The physical apparatus 800 of FIG. 8 comprises, in the illustratedembodiment, a substantially self-contained unit having, inter alia, acombined pressure transducer 422 and applanation device 400, motorcontrollers 811, RISC digital processor 808 with associated synchronousDRAM (SDRAM) memory 817 and instruction set (including scaling lookuptables), display LEDs 819, front panel input device 821, and powersupply 823. In this embodiment, the controllers 811 is used to controlthe operation of the combined pressure transducer/applanation device,with the control and scaling algorithms are implemented on a continuingbasis, based on initial operator/user inputs.

For example, in one embodiment, the user input interface comprises aplurality (e.g., two) buttons disposed on the face of the apparatushousing (not shown) and coupled to the LCD display 879. The processorprogramming and LCD driver are configured to display interactive promptsvia the display 879 to the user upon depression of each of the twobuttons. For example, in the present context, one button is assigned asthe “weight range” button, wherein when depressed, the LCD display 879prompts the user to select from one of a plurality of discrete weightranges. Similarly, the other button is assigned the “height range”function, wherein its depression prompts the user via the display toselect one of a plurality of height ranges. Once these two values havebeen entered, the apparatus 800 automatically determines the PP aspreviously described, and uses the two inputs to calculate BMI, which isthen automatically ratioed to the PP to generate a scaling factor. Suchdisplay and control functions are well within the capability of those ofordinary skill in the electronic arts, and accordingly are not describedfurther herein.

Furthermore, a patient monitor (PM) interface circuit 891 shown in FIG.8 may be used to interface the apparatus 800 to an external orthird-party patient monitoring system. Exemplary configurations for suchinterfaces 891 are described in detail in co-pending U.S. patentapplication Ser. No. 10/060,646 entitled “Apparatus and Method forInterfacing Time-Variant Signals” filed Jan. 30, 2002, and assigned tothe Assignee hereof, which is incorporated by reference herein in itsentirety, although other approaches and circuits may be used. Thereferenced interface circuit has the distinct advantage of automaticallyinterfacing with literally any type of patient monitor system regardlessof its configuration. In this fashion, the apparatus 800 of the presentinvention coupled to the aforementioned interface circuit allowsclinicians and other health care professionals to plug the apparatusinto in situ monitoring equipment already on hand at their facility,thereby obviating the need (and cost) associated with a dedicatedmonitoring system just for blood pressure measurement.

Additionally, an EEPROM 852 is physically coupled to the pressuretransducer 422 as shown in FIGS. 8 and 8 a, so as to form a unitary unit850 which is removable from the host apparatus 800. The details of theconstruction and operation of such coupled assemblies are described indetail in co-pending U.S. application Ser. No. 09/652,626, entitled“Smart Physiologic Parameter Sensor and Method”, filed Aug. 31, 2000,assigned to the Assignee hereof, and incorporated by reference herein inits entirety.

By using such a coupled and removable arrangement, both the transducer422 and EEPROM 852 may be readily removed and replaced within the system800 by the operator. Referring to the scaling methodologies previouslydescribed herein (e.g., BMI/PP and BMI/WC), the discrete scaling rangesare advantageously correlated to the unitary assembly 850 such thatdifferent assemblies are used for different scaling ranges. For example,in the context of the BMI/WC method as shown best in Table 1 above,three unitary assemblies 850 are provided, one corresponding to eachrange of scale index I_(s). The EEPROM 852 of each assembly 850 isaccordingly coded with the appropriate scale factor(s) corresponding tothat scale index I_(s), and is also visually coded (e.g., by color). Theuser/operator selects the appropriate assembly 850 based on the BMI/WC(scale index) value obtained from the subject to be monitored, andinserts the assembly 850 into the apparatus 800. Scaling factors orrelated data present in the EEPROM 852 are retrieved from the EEPROM,and applied to the unsealed waveform (after applanation level, etc., areoptimized as previously described herein) to produce a scaled output.This approach has the benefit of obviating the input or selection ofdata on the system by the operator; the operator simply determines thescale index value (such as by nomograph or calculator), and then selectsthe appropriate assembly 750 based on color (or textual information onthe assembly or its package).

It will be recognized that the use of a limited number oftransducer/EEPROM assemblies may be readily applied to the BMI/PPmethodology previously described as well. For example, the full range ofBMI/PP can be divided into n=0, 1, 2 . . . discrete intervals (whetherlinearly or in companded fashion), with a separate assembly 850 for eachinterval. The EEPROM 852 for each assembly will then contain the scalingdata applicable to that interval, such scaling data being for example ascaling function segment, “stretch” factor, or similar. As yet anotheralternative, the assemblies 850 can be coded based purely on BMI value,thereby alleviating the operator from determining PP and calculatingBMI/PP. Numerous other such variants are possible, all considered tofall within the scope of the present invention.

It is also noted that the apparatus 800 described herein may beconstructed in a variety of different configurations, and using avariety of different components other than those specifically describedherein. The construction and operation of such apparatus (given thedisclosure provided herein) are readily within the possession of thoseof ordinary skill in the medical instrumentation and electronics field,and accordingly not described further herein.

The computer program(s) for implementing the aforementioned methods ofhemodynamic assessment using optimal applanation and scaling is/are alsoincluded in the apparatus 800. In one exemplary embodiment, the computerprogram comprises an object (“machine”) code representation of a C⁺⁺source code listing implementing the methodology of FIGS. 5 d-5 i,either individually or in combination thereof. While C⁺⁺ language isused for the present embodiment, it will be appreciated that otherprogramming languages may be used, including for example VisualBasic™,Fortran, and C. The object code representation of the source codelisting is compiled and may be disposed on a media storage device of thetype well known in the computer arts. Such media storage devices caninclude, without limitation, optical discs, CD ROMs, magnetic floppydisks or “hard” drives, tape drives, or even magnetic bubble memory. Thecomputer program further comprises a graphical user interface (GUI) ofthe type well known in the programming arts, which is operativelycoupled to the display and input device of the host computer orapparatus on which the program is run.

In terms of general structure, the program is comprised of a series ofsubroutines or algorithms for implementing the applanation and scalingmethodologies described herein based on measured parametric dataprovided to the host apparatus 800. Specifically, the computer programcomprises an assembly language/micro-coded instruction set disposedwithin the embedded storage device, i.e. program memory, of the digitalprocessor or microprocessor associated with the hemodynamic measurementapparatus 800. This latter embodiment provides the advantage ofcompactness in that it obviates the need for a stand-alone PC or similarhardware to implement the program's functionality. Such compactness ishighly desirable in the clinical and home settings, where space (andease of operation) are at a premium.

Method of Providing Treatment

Referring now to FIG. 9, a method of providing treatment to a subjectusing the aforementioned methods is disclosed. As illustrated in FIG. 9,the first step 902 of the method 900 comprises selecting the bloodvessel and location to be monitored. For most human subjects, this willcomprise the radial artery (as monitored on the inner portion of thewrist), although other locations may be used in cases where the radialartery is compromised or otherwise not available.

Next, in step 904, the applanation mechanism 400 is placed in the properlocation with respect to the subject's blood vessel. Such placement maybe accomplished manually, i.e., by the caregiver or subject by visuallyaligning the transducer and device over the interior portion of thewrist, by the pressure/electronic/acoustic methods of positioningpreviously referenced, or by other means. Next, the first applanationelement 402 is operated per step 906 so as to applanate the tissuesurrounding the blood vessel to a desired level so as to identify anoptimal position where the effects of transfer loss and other errorsassociated with the tonometric measurement are mitigated. The priordiscussion regarding FIG. 5 herein illustrates one exemplary method offinding this optimum applanation level.

Once the optimal level of applanation for the applanator element 402 isset, the pressure waveform is measured per step 908, and the relevantdata processed and stored as required (step 910). Such processing mayinclude, for example, calculation of the pulse pressure (systolic minusdiastolic), calculation of mean pressures or mean values over finitetime intervals, and optional scaling of the measured pressurewaveform(s). One or more resulting outputs (e.g., systolic and diastolicpressures, pulse pressure, mean pressure, etc.) are then generated instep 912 based on the analyses performed in step 910. The relevantportions of the process is then repeated (step 914) if desired so as toprovide continuous monitoring and evaluation of the subject's bloodpressure.

Lastly, in step 916, the “corrected” measurement of the hemodynamicparameter (e.g., systolic and/or diastolic blood pressure) is used asthe basis for providing treatment to the subject. For example, thecorrected systolic and diastolic blood pressure values are generated anddisplayed or otherwise provided to the health care provider in realtime, such as during surgery. Alternatively, such measurements may becollected over an extended period of time and analyzed for long termtrends in the condition or response of the circulatory system of thesubject. Pharmacological agents or other courses of treatment may beprescribed based on the resulting blood pressure measurements, as iswell known in the medical arts. Similarly, in that the present inventionprovides for continuous blood pressure measurement, the effects of suchpharmacological agents on the subject's physiology can be monitored inreal time.

It is noted that many variations of the methods described above may beutilized consistent with the present invention. Specifically, certainsteps are optional and may be performed or deleted as desired.Similarly, other steps (such as additional data sampling, processing,filtration, calibration, or mathematical analysis for example) may beadded to the foregoing embodiments. Additionally, the order ofperformance of certain steps may be permuted, or performed in parallel(or series) if desired. Hence, the foregoing embodiments are merelyillustrative of the broader methods of the invention disclosed herein.

While the above detailed description has shown, described, and pointedout novel features of the invention as applied to various embodiments,it will be understood that various omissions, substitutions, and changesin the form and details of the device or process illustrated may be madeby those skilled in the art without departing from the spirit of theinvention. The foregoing description is of the best mode presentlycontemplated of carrying out the invention. This description is in noway meant to be limiting, but rather should be taken as illustrative ofthe general principles of the invention. The scope of the inventionshould be determined with reference to the claims.

1.-74. (canceled)
 75. A method of measuring the pulse pressure of aliving subject, comprising: obtaining via pressure sensor a plurality ofpressure values associated with a blood vessel of said living subject;deriving a scaling factor based on at least one physiological parameter;using at least one algorithm run on a processor associated with saidpressure sensor to scale said plurality of pressure values using saidscaling factor; and utilizing at least said scaled pressure values togenerate a pulse pressure value of said living subject.
 76. The methodof claim 75, wherein said at least one physiological parameter scalingfactor is based on at least one of body mass index (BMI) and/or wristcircumference (WC).
 77. The method of claim 76, wherein said act ofobtaining said plurality of pressure values comprises applanating saidblood vessel of said living subject via said pressure sensor.
 78. Themethod of claim 77, wherein said living subject comprises a human being,and said act of applanating is performed substantially contemporaneouslywith said act of measuring said plurality of pressure values. 79.Apparatus adapted to measure the pressure of a blood vessel of a livingsubject, comprising: a digital processor; a pressure sensor adapted togenerate a signal relating to pressure applied thereto; and at least onecomputer program configured to run on the digital processor and furtherconfigured to scale said signal using a scaling factor based at least inpart on a derived parameter particularly associated with the physiologyof said subject.
 80. The apparatus of claim 79, further comprising abias element disposed proximate to said pressure sensor and adapted tomitigate the effects of tissue interposed between said sensor and saidblood vessel, said bias element substantially surrounding at least aportion of said pressure sensor.
 81. The apparatus of claim 79, furthercomprising an applanation apparatus adapted to controllably press atleast a portion of said pressure sensor and said bias element againstsaid tissue.
 82. The apparatus of claim 79, wherein said signalsrelating to said pressure comprise a measurement of systolic anddiastolic pressure of said subject.
 83. The apparatus of claim 79,wherein said derived parameter particularly associated with said subjectcomprises body mass index.
 84. The apparatus of claim 83, furthercomprising a user interface operative to receive data entered by a user,said data relating to at least said body mass index.
 85. The apparatusof claim 79, wherein said living subject comprises a human being, andsaid bias element uses at least said pressure sensor to at least partlyapplanate the radial artery of said human being, said at least partialapplanation being performed while said signal is being generated.
 86. Amethod of measuring the pulse pressure of a living subject, comprising:utilizing a pressure sensor to obtain a plurality of pressure valuesassociated with a systolic and diastolic pressure of a blood vessel ofsaid living subject; utilizing said plurality of pressure values todetermine a pulse pressure of said living subject; deriving a scalingfactor based at least in part on at least one physiologic parameter;scaling said determined pulse pressure using said scaling factor usingat least one algorithm run on a processor associated with said pressuresensor; and presenting said scaled pulse pressure to a user.
 87. Themethod of claim 86, wherein said at least one physiological parametercomprises a body mass index (BIM of said subject.
 88. The method ofclaim 87, wherein said act of determining said derivation of saidscaling factor comprises utilizing one or more inputs received from auser via a user interface.
 89. A method of measuring the pulse pressureof a living subject, comprising: utilizing a pressure sensor to measurea plurality of pressure values of a blood vessel of said living subject;determining a physiological parameter of said living subject; deriving ascaling factor based at least in part on said physiological parameter;scaling said plurality of pressure values using said scaling factor; andutilizing said scaled pressure values to generate at least one pulsatilepressure value.
 90. The method of claim 89, wherein said firstphysiological parameter comprises body mass index (BMI).
 91. The methodof claim 89, wherein said first physiological parameter comprises wristcircumference (WC).
 92. The method of claim 89, wherein said act ofutilizing a pressure sensor measure said plurality of pressure values ofa blood vessel comprises obtaining a tonometric measurement of asystolic and diastolic pressure of said living subject.
 93. Apparatusfor measuring the pulse pressure of a living subject, comprising: afirst means for generating a signal relating to pressure in a bloodvessel of said subject; a second means for scaling said signal using ascaling factor, said scaling factor comprising a value derived from atleast one physiological parameter of said subject; and a third means foroutputting as a value for said pulse pressure said scaled signal. 94.The apparatus of claim 93, wherein said signal is affected at least inpart by tissue interposed between said first means and a blood vessel ofsaid subject, and said apparatus further comprises a fourth means formitigating the effects of said tissue on said signal, said first andfourth means being disposed proximate to one another.
 95. The apparatusof claim 94, further comprising a means for controllably pressing atleast a portion of said first and fourth means against said tissue. 96.The apparatus of claim 93, wherein further comprising a bias elementsubstantially enveloping at least a portion of said first means.
 97. Theapparatus of claim 93, wherein said at least one physiological parametercomprises body mass index (BMI), and said apparatus further comprises ameans for receiving data relating to said subject's weight and saidsubject's height from a user, said BMI being calculated from said weightand height data.
 98. The apparatus of claim 93, wherein saidphysiological parameter comprises wrist circumference.
 99. The apparatusof claim 96, wherein said living subject comprises a human being, andsaid apparatus uses at least said bias element to at least partlyapplanate the radial artery of said human being, said at least partialapplanation being performed while said signal is being generated.